..These data are interpreted to suggest that peroxynitrite ions are involved in the etiopathogenesis of Parkinson's disease, and metallothionein-mediated coenzyme Q10 synthesis may provide neuroprotection...

..These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection...

Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases

Manuchair EbadiDepartment of Pharmacology, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58203, USACurr Drug Targets 7:1513-29. 2006

..Its therapeutic efficacy in Alzheimer's disease remains uncertain. In Alzheimer's disease, short term studies of selegiline suggest a beneficial effect; whereas long term studies are less convincing...

Neuroprotective actions of selegiline

M EbadiDepartment of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USAJ Neurosci Res 67:285-9. 2002

..Most of the aforementioned properties occur independently of selegiline's efficacy to inhibit MAO-B...

Shaik ShavaliDepartment of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USAJ Neurosci Res 76:563-71. 2004

..Taken together, these results suggest that alpha-syn up-regulation and oxidative stress are contributing factors in 1BnTIQ-induced neurotoxicity in dopaminergic neurons in PD...

P SangchotDepartment of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, N D 58203, USADev Neurosci 24:143-53. 2002

..However, in the absence of excess iron, DFO itself may have deleterious effects on the morphology and hence integrity of dopaminergic neurons...

Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein

Sawitri WanpenDepartment of Pharmacology, Physiology and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202, USABrain Res 1005:67-76. 2004

..Furthermore, MT overexpression may protect dopaminergic neurons against salsolinol-induced neurotoxicity, most probably by the inhibition of oxidative stress and apoptotic pathways including caspase-3 activation...

Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronal cells in co-culture: relevance to Parkinson's disease

Shaik ShavaliDepartment of Pharmacology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USANeurochem Res 31:85-94. 2006

..These results suggest that reactive microglias could induce oxidative stress in dopaminergic neurons and such oxidative stress may finally lead to nitration of alpha-synuclein and death of dopaminergic neurons in PD...

..Therefore, future research may synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics...

Peroxynitrite in the pathogenesis of Parkinson's disease and the neuroprotective role of metallothioneins

..These studies provide evidence that nitric oxide synthase activation and peroxynitrite ion overproduction may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection...

Jaturaporn ChagkutipDepartments of Pharmacology and of Neurosciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, 58202, USANeurochem Res 30:633-9. 2005

..These effects of MPP+ result in the generation of ROS, which may be involved in neuronal degeneration seen in Parkinson's disease...

Radiation safety and quality control in the cyclotron laboratory

Sushil SharmaPositron Imaging Research Laboratory, Center of Excellence in Neurosciences, University of North Dakota, School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, USARadiat Prot Dosimetry 118:431-9. 2006

....

Attenuation of cocaine and methamphetamine neurotoxicity by coenzyme Q10

Sirirat KlongpanichapakDepartment of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, ND, 58203, USANeurochem Res 31:303-11. 2006

Sushil SharmaCyclotron and Positron Imaging Research Laboratory, Center of Excellence in Neurosciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USANeurochem Int 52:352-62. 2008

..It is envisaged that high-resolution SPECT imaging system will further improve in vivo non-invasive translational research on CNS disorders of unknown etiopathogenesis and their treatment in future...

Shaik ShavaliDepartment of Pathology, University of North Dakota, School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58202, USANeurosci Lett 439:125-8. 2008

..This study has implications to the pathogenesis of familial PD where alpha-syn overexpression is mainly involved...

Dopamine agonist 3-PPP fails to protect against MPTP-induced toxicity

Dhanasekaran MuralikrishnanDepartment of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USANeurochem Res 29:379-84. 2004

..3-PPP had no effect on the SH-SY5Y neuronal cell growth in culture and did not block the MPP(+)-induced cytotoxicity. This study shows that the dopamine agonist 3-PPP failed to protect against MPTP-induced dopaminergic neurotoxicity...

..It is envisaged that in addition to coenzyme Q homologues, the improved method could be utilized for the multiple analyses of DNA, RNA and proteins from clinically significant biopsy and autopsy samples...

Effect of MPTP on Dopamine metabolism in Ames dwarf mice

Dhanasekaran MuralikrishnanDepartment of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USANeurochem Res 27:457-64. 2002

..This study shows that the MAO activity and the coenzyme content of dwarf mice are similar to those of their wild-type controls and hence susceptible to MPTP-induced toxicity...

P GovitrapongDepartment of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USAJ Pineal Res 35:16-23. 2003

..These results indicate that a high affinity dopamine transporter exists in the bovine pineal, which may exhibit circadian periodicity, and whose physiological functions need to be delineated and characterized in future investigations...

Sunitha BollimunthaDepartment of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USAJ Biol Chem 280:2132-40. 2005

..As a result, these studies represent the first description of an agonist-dependent relationship between a small heat shock protein and beta-arrestin to form a previously unknown antiapoptotic "signalosome."..

..Ebselen did not induce any behavioral changes and did not block MPTP-induced tremor and akinesia. Ebselen had no effect on the monoamine oxidase activity and did not protect against MPTP-induced dopamine depletion in striatum...

..The decrease of zinc-positive neuronal terminal fields in the striatum after MPP+ administration is most likely due to a neuronal release of vesicular zinc in response to its dopaminergic neurotoxicity...

..In summary, these results suggested that alpha-ZAL may effectively preserve Hcy-induced decrease in NO, increase in ET-1/NO ratio and apoptosis, which contributes to protective effects of phytoestrogens on endothelial function...

Effects of D1- and D2-dopamine receptor activation on melatonin synthesis in bovine pinealocytes

..Moreover, post-treatment with insulin inhibited caspase-3 activation and loss of cell viability in NONOate- but not in SIN-1-exposed cells. These findings suggest that NO is a potent toxin independent of peroxynitrite formation...

Research Grants13

..Therefore, future research must synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics. ..

..The completion of these studies will undoubtedly provide additional items of information on reactive oxygen species-induced damage of mitochondrial DNA and the protective effects of coenzyme Q10(ubiquinol) to minimize it. ..